Immunologic Interplay Between HIV/AIDS and COVID-19: Adding Fuel to the Flames?

Abstract

Purpose of review: HIV/AIDS and COVID-19 have been the major pandemics overwhelming our times. Given the enduring immune disfunction featuring people living with HIV (PLWH) despite combination antiretroviral therapy (cART), concerns for higher incidence and severity of SARS-CoV-2 infection as well as for suboptimal responses to the newly developed vaccines in this population arose early during the pandemics. Herein, we discuss the complex interplay between HIV and SARS-CoV-2, with a special focus on the immune responses to SARS-CoV-2 natural infection and vaccination in PLWH.

Recent findings: Overall, current literature shows that COVID-19 severity and outcomes may be worse and immune responses to infection or vaccination lower in PLWH with poor CD4 + T-cell counts and/or uncontrolled HIV viremia. Data regarding the risk of post-acute sequelae of SARS-CoV-2 infection (PASC) among PLWH are extremely scarce, yet they seem to suggest a higher incidence of such condition. Scarce immunovirological control appears to be the major driver of weak immune responses to SARS-CoV-2 infection/vaccination and worse COVID-19 outcomes in PLWH. Therefore, such individuals should be prioritized for vaccination and should receive additional vaccine doses. Furthermore, given the potentially higher risk of developing long-term sequelae, PLWH who experienced COVID-19 should be ensured a more careful and prolonged follow-up.

Keywords: AIDS; COVID-19; HIV; Immune responses; SARS-CoV-2; Vaccines.

Fig. 1

Immune responses to SARS-CoV-2 infection in PLWH. A Chronic HIV infection on cART drives a strong constitutive IFN-I signaling within absorptive enterocytes in the small intestine, which, however, is not able to prevent SARS-CoV-2 infection in this compartment. The interplay between HIV and SARS-CoV-2 in modulating IFNs-I responses in other anatomical sites, especially the respiratory tract, which is the site of initial infection, is currently unknown. B PLWH with well-controlled HIV infection mount adaptive immune responses comparable to those of people without HIV. Yet, PLWH with low CD4 + T-cell counts and/or detectable HIV viremia develop suboptimal immune responses to SARS-CoV-2 infection (fewer and exhausted SARS-CoV-2–specific T-cells, impaired T-cell cross recognition of VOCs, lower SARS-CoV-2–specific B-cells and neutralizing antibodies). C HIV infection is associated with enduring systemic inflammation and immune activation despite effective cART; on the other side, in absence of cART, HIV infection leads to immune suppression, mainly—albeit not only—driven by the depletion of CD4 + T-cells. Whether such features of HIV infection may exacerbate or hinder the COVID-19–related cytokine storm is currently unknown, as the few available data are conflicting. D PLWH with low CD4 + T-cell counts may have a delayed SARS-CoV-2 clearance due to the immune defects. The subsequent prolonged viral replication (sustained by the RNA-dependent RNA-polymerase) can lead to the emergence of multiple mutations and thus to the development of new viral variants escaping from antibody neutralization. PLWH, people living with HIV; cART, combination antiretroviral therapy; IFN-I, type-I interferon; VOCs, variants of concern. Created with BioRender.com

Fig. 2

Interplay between HIV infection and immune responses to SARS-CoV-2 infection and vaccination. PLWH with well-controlled HIV infection on cART (suppressed HIV viremia and full recovery of CD4 + T-cell counts) mount adequate adaptive immune responses to both SARS-CoV-2 infection and vaccination, which lend protection against the severe forms of the disease and from future infections/reinfections. On the contrary, ongoing HIV replication and immunodeficiency with low CD4 + T-cell counts hamper the development of both T-cell and humoral memory in response to SARS-CoV-2 infection and vaccination, thus explaining the increased risk of severe COVID-19 and breakthrough infections in PLWH with scarce immunovirological control. Created with BioRender.com